Yinghua Zhang M.D., Ph.D.

Personal History:

I completed my MD degree at the Sun Yat-sen University of Medical Sciences, P.R. China and my PhD degree in Molecular Biology and Genetics at Kyoto Prefectureal University of Medicine in Japan. Then I got my postdoctoral traning in cancer biology at Lombardi cancer center of Georgetown University.

Research Interests:

Spectrin is an actin-binding protein composed of a 280 kDa Î±-subunit and a 246 kDa beta-subunit, which associate laterally to form an elongated heterodimer. Two such dimers self-associate, head to head, to form a heterotetramer. Spectrin and its associated proteins function to stabilize membranes and organize proteins and lipids into microdomains in intracellular organelles and at the plasma membrane. In cardiac muscle, these proteins bind to and stabilize the t-tubular and SR membranes. We have studied intracellular spectrins in the heart to test the hypothesis that separate spectrin cytoskeletal structures stabilize t-tubules and SR, and that their association with these membranes is regulated by phosphorylation. My research has examined two alternatively spliced forms of Î±II-spectrin, one with a 20 amino acid insert in the SH3 domain just C-terminal to repeat 10 (termed SH3i+), and a 21 amino acid insert close to the C-terminus, in the nucleation site for binding to the beta-subunit (termed â?ocardi+). My studies show that both alternatively spliced forms of these proteins are developmentally regulated, that their expression is independent of other alternatively spliced sequences, and that their solubility and membrane association is regulated by phosphorylation. The SH3i+ form appears to associate preferentially with the SR, where it binds to ankyrin B, RyR and SERCA. Dissociation of the SH3i+ form of the protein from membranes and its appearance in the soluble fraction is promoted by calyculin A (which inhibits dephosphorylation) and alters EC-coupling in cardiomyocytes. Inclusion of the alternatively spliced, cardi+ sequence into Î±II-spectrin has no significant effect on binding to either betaI- or betaII-spectrin, but it does appear to limit the amount of Î±II-spectrin that is available for binding. I am still testing the possibility that the cardi+ form associates preferentially with the t-tubule, where it may associate preferentially with the Na,K-ATPase and the Na,Ca-exchanger and the physiological consequences of its phosphorylation.